hirudin and Aortic-Valve-Stenosis

Bivalirudin may be an effective anticoagulation alternative to heparin as anticoagulant agent in percutaneous transcatheter aortic valve interventions (PAVI). We aimed to compare safety and efficacy of bivalirudin versus heparin as the procedural anticoagulant agent in patients undergoing PAVI.. We conducted an electronic database search of all published data. The primary efficacy endpoints were all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. Safety endpoints include major and life-threatening bleed according to VARC and BARC bleeding, blood transfusion, vascular complications, and acute kidney injury. Odds ratios (OR) and 95% confidence intervals (CI) computed using the Mantel-Haenszel method.. Three studies (n = 1690 patients) were included, one randomized trial and two observational studies. There was a significant difference favoring bivalirudin over heparin for myocardial infarction (OR 0.41, 95%CI 0.20-0.87). There was no significant difference in all-cause mortality at 30 days (OR 0.97, 95%CI 0.62-1.52), cardiovascular mortality (OR 1.03, 95%CI 0.52-2.05), stroke (OR 1.23, 95%CI 0.62-2.46), vascular complications (OR 0.96, 95%CI 0.70-1.32), acute kidney injury (OR 1.03, 95%CI 0.53-2.00), blood transfusion (OR 0.67, 95% CI 0.45-1.01), major and life-threatening bleed (OR 0.74, 95%CI 0.37-1.49), and BARC bleeding (OR 0.52, 95%CI 0.23-1.18).. In patient undergoing aortic valve interventions, no difference was seen between the use of bivalirudin and heparin as the procedural anticoagulant agent, except for a significant lower myocardial infarction events when bivalirudin was used. Further large randomized trials are needed to confirm current results.

Topics: Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Balloon Valvuloplasty; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thromboembolism; Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement (TAVR) is considered an important option in the management of patients with critical aortic valve stenosis that are either inoperable or have a high surgical risk. Despite continued advances in the procedural aspects of TAVR and decreasing complications rates, the risks of major vascular complications and stroke remain significant, which may in turn confer worse clinical outcomes and impact morbidity and mortality. In this review, we outline certain limitations of the currently recommended periprocedural anticoagulation in TAVR, namely unfractionated heparin that is guided by activated clotting times and protamine use if the bleeding risk is high. We will explore the potential for bivalirudin in this setting, which has become a frontrunner in acute coronary syndrome management because of favorable pharmacokinetics and lower bleeding complications. Finally, we will describe an ongoing large multicenter multinational trial that compares intravenous bivalirudin to unfractionated heparin during TAVR procedures using standardized clinical endpoints.

Topics: Aged; Aged, 80 and over; Antithrombins; Aortic Valve Stenosis; Cardiac Catheterization; Clinical Trials as Topic; Female; Heart Valve Prosthesis; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins

TandemHeart is a recently-introduced percutaneous left ventricular assist device that can be used for hemodynamic support during high-risk interventional procedures in severely compromised patients. Angioplasty and stent placement in patients with coronary artery disease and high-risk coronary anatomy including the left main coronary artery have been described using this device. We report the first human case description of a high-risk percutaneous balloon aortic valvuloplasty for critical bicuspid aortic stenosis using the TandemHeart for periprocedural hemodynamic support. Also not previously reported is the use of bivaluridin as the periprocedural antithrombin agent during and after high-risk aortic valvuloplasty.

Topics: Angioplasty, Balloon; Anticoagulants; Aortic Valve Stenosis; Cardiac Catheterization; Echocardiography, Transesophageal; Follow-Up Studies; Heart-Assist Devices; Hirudins; Humans; Intra-Aortic Balloon Pumping; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Risk Assessment; Severity of Illness Index; Stroke Volume; Treatment Outcome

Selection of valve type and procedural anticoagulant may impact bleeding and vascular complications in transfemoral transcatheter aortic valve replacement (TAVR). We sought to compare outcomes by valve [balloon expandable (BE) or non-BE] and anticoagulant [bivalirudin vs. unfractionated heparin (UFH)] type from the BRAVO-3 trial.. BRAVO-3 was a randomized multicenter trial including 500 BE-TAVR and 282 non-BE TAVR patients, randomized to bivalirudin versus UFH. Selection of valve type was at the discretion of the operator but randomization was stratified according to valve type. Total follow up was to 30 days. We examined the incidence of Bleeding Academic Research Consortium type ≥3b bleeding, major vascular complications and all ischemic outcomes at 30-days. Outcomes were adjusted using logistic regression analysis.. Of the trial cohort, 63.9% were treated with BE valves (n = 251 bivalirudin vs. n = 249 UFH) and 36.1% with non-BE valves (n = 140 bivalirudin vs. n = 142 UFH). Patients treated with non-BE valves were older, with higher euroSCORE I. At 30 days, there were nonsignificant differences between the two valve types for adjusted risk of all-cause death (HR 2.07, 95% CI 0.91-4.70, P = 0.084) and major vascular complications (HR 1.78, 95% CI 0.97-3.26, P = 0.062) with non-BE compared with BE valves, but all other outcomes were similar. A significant interaction was observed between valve and anticoagulant type, with lower risk of major vascular complications with bivalirudin compared with UFH in non-BE TAVR (P-interaction = 0.039).. Majority of patients in the BRAVO 3 trial received BE valves. At 30-days, adjusted risk of clinical outcomes was similar with non-BE vs. BE valves. A significant interaction was observed between valve type and procedural anticoagulant for lower risk of major vascular complications with bivalirudin versus UFH in non-BE TAVR.

Topics: Aged, 80 and over; Antithrombins; Aortic Valve; Aortic Valve Stenosis; Cause of Death; Dose-Response Relationship, Drug; Europe; Female; Fibrinolytic Agents; Follow-Up Studies; Heart Valve Prosthesis; Heparin; Hirudins; Humans; Incidence; Infusions, Intravenous; Male; Peptide Fragments; Practice Guidelines as Topic; Prosthesis Design; Recombinant Proteins; Retrospective Studies; Survival Rate; Thrombolytic Therapy; Thrombosis; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; United States

Cerebral embolization is a frequent complication after transcatheter aortic valve replacement (TAVR). We hypothesized that cerebral embolization may be reduced by anticoagulation with bivalirudin during TAVR.. This study sought to determine the proportion of patients with new cerebral embolus after TAVR and to investigate whether parenteral procedural anticoagulation strategies affect cerebral embolization.. The BRAVO (Effect of Bivalirudin on Aortic Valve Intervention Outcomes)-3 randomized trial compared bivalirudin with unfractionated heparin in patients undergoing transfemoral TAVR. A prospective cerebral magnetic resonance imaging (MRI) substudy was conducted in 4 sites; 60 patients were imaged with brain MRI after TAVR. Primary endpoint was proportion of patients with new cerebral emboli on MRI. Secondary endpoints included quantitative MRI analyses of cerebral lesions and neurological outcomes at 48 h and 30 days.. Patients were randomized to bivalirudin (n = 29) versus heparin (n = 31). The proportion of patients with new cerebral emboli on MRI did not differ between bivalirudin and heparin groups (65.5% vs. 58.1%; p = 0.55). Groups were similar for median number of emboli per patient (1 [interquartile range (IQR): 0 to 3] vs. 1 [IQR: 0 to 1]; p = 0.08), total volume of emboli (45 [IQR: 0 to 175] mm(3) vs. 33 [IQR: 0 to 133] mm(3); p = 0.86), or proportion of patients with a clinical neurological deficit at 48 h or 30 days. All patients who presented clinically with stroke had evidence of new emboli on MRI.. This study documented cerebral embolization in nearly two-thirds of patients during contemporary TAVR. There were no significant differences in cerebral embolization for bivalirudin versus heparin anticoagulation during TAVR. (Open-Label, Randomized Trial in Patients Undergoing TAVR to Determine Safety and Efficacy of Bivalrudin vs. UFH [BRAVO-2/3]; NCT01651780).

Topics: Aged, 80 and over; Antithrombins; Aortic Valve Stenosis; Brain; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hirudins; Humans; Intracranial Embolism; Intraoperative Complications; Magnetic Resonance Imaging; Male; Peptide Fragments; Prospective Studies; Recombinant Proteins; Transcatheter Aortic Valve Replacement

Anticoagulation is required during transcatheter aortic valve replacement (TAVR) procedures. Although an optimal regimen has not been determined, heparin is mainly used. Direct thrombin inhibition with bivalirudin may be an effective alternative to heparin as the procedural anticoagulant agent in this setting.. The goal of this study was to determine whether bivalirudin offers an alternative to heparin as the procedural anticoagulant agent in patients undergoing TAVR.. A total of 802 patients with aortic stenosis were randomized to undergo transfemoral TAVR with bivalirudin versus unfractionated heparin during the procedure. The 2 primary endpoints were major bleeding within 48 h or before hospital discharge (whichever occurred first) and 30-day net adverse clinical events, defined as the combination of major adverse cardiovascular events (all-cause mortality, myocardial infarction, or stroke) and major bleeding.. Anticoagulation with bivalirudin versus heparin did not meet superiority because it did not result in significantly lower rates of major bleeding at 48 h (6.9% vs. 9.0%; relative risk: 0.77; 95% confidence interval [CI]: 0.48 to 1.23; p = 0.27) or net adverse cardiovascular events at 30 days (14.4% vs. 16.1%; relative risk: 0.89; 95% CI: 0.64 to 1.24; risk difference: -1.72; 95% CI: -6.70 to 3.25; p = 0.50); regarding the latter, the prespecified noninferiority hypothesis was met (pnoninferiority < 0.01). Rates of major adverse cardiovascular events at 48 h were not significantly different (3.5% vs. 4.8%; relative risk: 0.73; 95% CI: 0.37 to 1.43; p = 0.35). At 48 h, the bivalirudin group had significantly fewer myocardial infarctions but more acute kidney injury events than the heparin group; at 30 days, these differences were no longer significant.. In this randomized trial of TAVR procedural pharmacotherapy, bivalirudin did not reduce rates of major bleeding at 48 h or net adverse cardiovascular events within 30 days compared with heparin. Although superiority was not shown, the noninferiority hypothesis was met with respect to the latter factor. Given the lower cost, heparin should remain the standard of care, and bivalirudin can be an alternative anticoagulant option in patients unable to receive heparin in TAVR. (International, Multi-center, Open-label, Randomized Controlled Trial in Patients Undergoing TAVR to Determine the Treatment Effect [Both Safety and Efficacy] of Using Bivalirudin Instead of UFH [BRAVO-2/3]; NCT01651780).

Topics: Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve Stenosis; Dose-Response Relationship, Drug; Echocardiography; Europe; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Incidence; Male; Peptide Fragments; Postoperative Hemorrhage; Recombinant Proteins; Retrospective Studies; Survival Rate; Thromboembolism; Transcatheter Aortic Valve Replacement; Treatment Outcome; United States

This study sought to investigate the clinical outcomes of patients with and without peripheral artery disease (PAD) in the BRAVO-3 trial with respect to the effect of bivalirudin versus unfractionated heparin (UFH).. PAD is found frequently in patients undergoing transcatheter aortic valve replacement (TAVR) and is reported to confer an increased risk of adverse events. It is unknown whether patients with and without PAD may demonstrate a differential response to bivalirudin versus UFH.. BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or cerebrovascular accidents (CVA). Net adverse cardiovascular events (NACE) were a composite of major bleeding or MACE.. The total cohort included 119 patients with PAD. Vascular complications occurred significantly more frequently in patients with PAD both in-hospital (25.2 vs. 16.7%; OR 1.68) and at 30 days (29.4 vs. 17.3%; OR 1.99). No significant differences were observed regarding mortality, NACE, MACE, major bleeding or CVA with bivalirudin versus UFH among patients with or without PAD. In patients with PAD, bivalirudin was associated with an increased risk of minor vascular complications at 30 days.. Patients with PAD undergoing transfemoral TAVR did not exhibit an increased risk of any major adverse events, according to the procedural anticoagulant randomization. However, patients treated with Bivalirudin had significantly higher rates of minor vascular complications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve Stenosis; Catheterization, Peripheral; Cerebrovascular Disorders; Europe; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Male; Myocardial Infarction; North America; Peptide Fragments; Peripheral Arterial Disease; Punctures; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome

Clinicians use validated scores to risk-stratify patients undergoing transcatheter aortic valve replacement (TAVR). However, evaluation by the Heart Team often deems patients to be at higher risk than their formal scores suggest. We sought to assess clinical outcomes of TAVR patients defined as high-risk by the Heart Team's assessment versus the patient's logistic EuroSCORE (LES).. The BRAVO-3 trial randomized patients at high risk (LES ≥ 18, or deemed inoperable by the Heart Team) to TAVR with periprocedural anticoagulation with unfractionated heparin versus bivalirudin. Endpoints included net adverse cardiac events (NACE: the composite of all-cause mortality, MI, stroke, or bleeding), major adverse cardiovascular events (MACE: death, MI, or stroke), the individual components of MACE, major vascular complications, BARC ≥ 3b bleeding and VARC life-threatening bleeding at 30 days. We compared patients deemed high-risk based on LES ≥ 18 versus high-risk by the Heart Team despite lower LES.. A total of 467/800 (58.4%) patients were deemed high-risk by the Heart Team despite LES < 18. After multivariable analysis, there were no differences in the odds of endpoints between groups (NACE, OR. Patients undergoing TAVR and labeled high-risk by LES ≥ 18 or Heart Team assessment despite LES < 18 have comparable short-term outcomes. Assignment of high-risk status to over 50% of patients is attributable to Heart Team's clinical assessment.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve; Aortic Valve Stenosis; Clinical Decision-Making; Decision Support Techniques; Female; Hemodynamics; Heparin; Hirudins; Humans; Male; Patient Care Team; Patient Selection; Peptide Fragments; Postoperative Complications; Predictive Value of Tests; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Transcatheter Aortic Valve Replacement; Treatment Outcome

Topics: Aged, 80 and over; Antithrombins; Aortic Valve Stenosis; Fibrin; Hirudins; Humans; Intraoperative Complications; Male; Peptide Fragments; Polymerization; Recombinant Proteins; Thrombelastography; Transcatheter Aortic Valve Replacement

Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR.. BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women.. The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH.. There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve; Aortic Valve Stenosis; Cardiac Catheterization; Europe; Female; Heart Valve Prosthesis Implantation; Hemorrhage; Heparin; Hirudins; Humans; Male; Multicenter Studies as Topic; Myocardial Infarction; North America; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Factors; Sex Factors; Stroke; Time Factors; Treatment Outcome

The occurrence of lupus anticoagulant is associated with the hazard of developing an antiphospholipid syndrome, a severe prothrombotic condition which may particularly occur after major surgical trauma. This disease requires certain considerations regarding surgical strategy and anticoagulation management. We describe the perioperative management of a patient scheduled for elective aortic valve replacement and diagnosed for having antiphospholipid antibodies. The procedure was successfully performed using a minimally invasive approach via transapical aortic valve replacement and anticoagulation with the nonreversible short-acting direct thrombin Inhibitor bivalirudin.

Topics: Aged; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aortic Valve; Aortic Valve Stenosis; Cardiac Catheterization; Hirudins; Humans; Male; Minimally Invasive Surgical Procedures; Peptide Fragments; Perioperative Care; Recombinant Proteins; Transcatheter Aortic Valve Replacement

We aimed to compare safety and efficacy of the direct thrombin inhibitor bivalirudin with unfractionated heparin (UFH) during transcatheter aortic valve implantation (TAVI).. In this retrospective analysis, 461 patients underwent TAVI between 2007 and 2012; 339 patients received bivalirudin, and 122 patients received UFH. In the bivalirudin group, the Sapien XT valve was implanted in 159 (46.9%) patients, and 180 (53.1%) received a Medtronic CoreValve. In the UFH group, only the Medtronic CoreValve was implanted. The primary outcome of interest was the incidence of any bleeding. Secondary outcomes of interest were all-cause mortality and cardiovascular mortality at 72 hours after the procedure and at 30 days.. No significant difference between the groups was observed for life-threatening bleeding (2.4% for bivalirudin vs 3.3% for UFH; P = 0.59), major bleeding (8.3% vs 8.2%, respectively; P = 0.98) and minor bleeding (8.3% vs 7.4%, respectively; P = 0.76). At 72 hours after the procedure, all-cause mortality was 3.0% in the bivalirudin group and 3.3% for the UFH group (P = 0.88), whereas cardiovascular mortality was 3.0% in the bivalirudin group and 2.5% in the heparin group (P = 0.77). At 30 days, all-cause mortality was 5.3% vs 4.1% in the bivalirudin and heparin groups (P = 0.57) and cardiovascular mortality was 4.4% vs 2.5% (P = 0.33). Device success (Valve Academic Research Consortium 2 composite end point) was 94.0% in the bivalirudin-treated and 92.6% in the UFH-treated patients (P = 0.60). The early safety at 30 days was 85.3% in the bivalirudin-treated group compared with 83.6% in the UFH-treated group (P = 0.65).. Bivalirudin has a safety and efficacy profile similar to weight-adjusted UFH during the TAVI procedure.

Topics: Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve Stenosis; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome

Topics: Aortic Valve Stenosis; Female; Heparin; Hirudins; Humans; Male; Peptide Fragments; Thromboembolism

To determine the impact of suture-mediated vascular closure devices (VCDs) on net adverse clinical events (NACEs) after balloon aortic valvuloplasty (BAV).. Ischemic and bleeding complications are common following transfemoral BAV; however, previous studies have been single center and limited by varying definitions of major bleeding.. The Effect of Bivalirudin on Aortic Valve Intervention Outcomes (BRAVOs) study was a retrospective observational study conducted at two high-volume academic centers over a 6-year period designed to compare the effect of bivalirudin versus unfractionated heparin. This is a subanalysis of 428 consecutive patients who underwent BAV (with 10-13 French sheaths) to compare the effect of hemostasis with VCDs versus manual compression utilizing standardized definitions. NACE was defined as the composite of major bleeding and major adverse clinical events (MACEs). All events were adjudicated by an independent clinical events committee who were blinded to antithrombin use.. Preclosure was performed in 269 (62.8%) of patients. While bivalirudin was used more frequently in those with pre-closure (60.6% vs. 37.7%, P < 0.001), a history of prior BAV (11.1% vs. 3.6%, P = 0.04) and peripheral vascular disease (30.7% vs. 19.7%, P = 0.01) was more common in those not undergoing preclosure (n = 159, 37%). Other clinical and demographic features were well balanced between groups. Vascular closure was associated with a significant reduction in NACE (24.5% vs. 10.0% P < 0.001). Results remained significant after adjusting for baseline differences and bivalirudin use (OR 0.38, 95% CI: 0.21-0.68; P = 0.001).. Our study suggests that suture-mediated vascular closure is associated with a substantial reduction in NACE after transfemoral BAV. Large randomized clinical trials should be conducted to confirm our results.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve Stenosis; Balloon Valvuloplasty; Chi-Square Distribution; Equipment Design; Female; Femoral Artery; Florida; Hemorrhage; Hemostatic Techniques; Heparin; Hirudins; Hospitals, High-Volume; Humans; Logistic Models; Male; Multivariate Analysis; New York City; Odds Ratio; Peptide Fragments; Punctures; Recombinant Proteins; Retrospective Studies; Risk Factors; Suture Techniques; Treatment Outcome

We sought to assess if bivalirudin use during balloon aortic valvuloplasty (BAV) would affect clinical outcomes compared with heparin.. We compared the outcomes of consecutive patients who underwent elective or urgent BAV with intraprocedural use of bivalirudin or heparin at two high-volume centres. All in-hospital events post BAV were adjudicated by an independent, blinded clinical events committee. Of 427 patients, 223 patients (52.2%) received bivalirudin and 204 (47.8%) received heparin. Compared with patients who received heparin, patients who received bivalirudin had significantly less major bleeding (4.9% vs. 13.2%, p=0.003). Net adverse clinical events (NACE, major bleeding or major adverse cardiovascular events [MACE]) were also reduced (11.2% vs. 20.1%, p=0.01). There was no significant difference in the rates of MACE (mortality, myocardial infarction or stroke, 6.7% vs. 11.3%, p=0.1), or vascular complications (major, 2.7% vs. 2.0%; minor, 4.5% vs. 4.9%; p=0.83). After multivariate analysis controlling for vascular preclosure, the use of bivalirudin remained independently associated with reduced major bleeding (OR 0.37; 95% CI: 0.16 to 0.84; p=0.02) while the association was attenuated in propensity-adjusted analysis (OR 0.44, 95% CI: 0.18 to 1.07, p=0.08).. In this registry of patients with severe aortic stenosis, bivalirudin as compared to heparin resulted in improved in-hospital outcomes post BAV in terms of reduced major bleeding, similar MACE and reduced NACE. If verified in a randomised study and extended to the transcatheter aortic valve implantation (TAVI) population, these results might indicate a potential benefit for patients undergoing such procedures.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Valve Stenosis; Balloon Valvuloplasty; Female; Florida; Hemorrhage; Heparin; Hirudins; Hospitals, High-Volume; Humans; Logistic Models; Male; Multivariate Analysis; Myocardial Infarction; New York City; Odds Ratio; Peptide Fragments; Propensity Score; Recombinant Proteins; Registries; Retrospective Studies; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome

Bivalirudin is an accepted alternative to heparin for anticoagulation during select cardiac procedures. Its use has not been well described during transcatheter aortic valve replacement. Herein is the report of a transcatheter valve replacement case that was complicated by catastrophe and need for emergent cardiopulmonary bypass. A successful outcome was achieved. However, the inability to rapidly reverse the anticoagulation effect of bivalirudin proved troublesome, and that provides for a cautionary tale about its use during transcatheter valve replacement.

Topics: Aged, 80 and over; Anticoagulants; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cardiopulmonary Bypass; Dose-Response Relationship, Drug; Heart Valve Prosthesis; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Transcatheter Aortic Valve Replacement

Topics: Aged; Antithrombins; Aortic Valve Stenosis; Coronary Angiography; Coronary Thrombosis; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Heart Valve Prosthesis Implantation; Heparin; Hirudins; Humans; Intra-Aortic Balloon Pumping; Recombinant Proteins; Thrombocytopenia

Little is known with regard to efficacy of heparin as an adjunct to fibrinolytics under conditions of severe vascular damage. In this study, we compared the effects of unfractionated heparin (UH), low-molecular weight heparin (LMWH), and recombinant desulfohirudin (HIR) in combination with streptokinase (SK) in such settings.. We used an established rabbit model, in which thrombosis, critical stenosis, and vascular wall damage were introduced to a segment of the abdominal aorta and the effects of the respective therapies were assessed by time to patency (TTP in minutes), cumulative patency (CP (%)), lysis of original clot (CL (%)), and net clot accretion (NCA (%)). Treatments were administered over 90 min at the following doses: SK: 33,000 U/kg, UH: 125-250 U/kg, LMWH: 1.25-2.5 mg/kg, HIR: 0.25-0.55 mg/kg.. Unexpectedly, UH and LMWH had a paradoxical and detrimental effect on SK-mediated recanalization as measured by both TTP and CP. Thus, administration of SK vs. SK+UH or SK+LMWH resulted in TTP values of 43+/-8 min vs. 70+/-11 min (p<0.05) and 67+/-12 min. (p<0.08), respectively. For CP, the corresponding values were 21+/-7%, 0.5+/-0.3% and 9+/-8%. This delay in vessel recanalization occurred despite excessive systemic anticoagulation (activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT) ratios >6 and >34, respectively). Of interest, both heparinoids completely inhibited SK-induced fibrinogen consumption (FC). In contrast, recombinant desulfohirudin (HIR) shortened SK-induced TTP (4.97+/-0.81 min) without preserving fibrinogen.. Our findings suggest that caution needs to be exercised, when using the combination of SK and heparinoids for the treatment of arterial thrombosis under conditions of severe vascular damage and stenosis.

Topics: Animals; Aorta, Abdominal; Aortic Valve Stenosis; Disease Models, Animal; Drug Antagonism; Drug Therapy, Combination; Fibrinolysis; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Male; Rabbits; Recombinant Proteins; Streptokinase; Thrombosis; Time Factors; Vascular Patency

An 81-year-old man with previous syncopal episodes, progressive shortness of breath, pulmonary edema, severe calcific aortic stenosis, and a history of heparin-induced thrombocytopenia required aortic valve replacement. Bivalirudin, a thrombin-specific anticoagulant, was used in place of heparin. The patient received a 50 mg bivalirudin bolus followed by an infusion between 1.5 mg x kg(-1) x h(-1) and 1.75 mg x kg(-1) x h(-1). Adequate anticoagulation was readily obtained resulting in an uneventful cardiopulmonary bypass. Activated clotting time (ACT) values steadily declined after discontinuation of the bivalirudin infusion. Bivalirudin is a practical alternative to heparin during cardiac surgical procedures.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Cardiopulmonary Bypass; Heart Valve Prosthesis; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Whole Blood Coagulation Time

To report the case of a patient with HIT that received a prolonged infusion of r-hirudin (lepirudin; Refludan; Hoechst, France) before, during and after cardiopulmonary bypass (CPB) for aortic surgery. Although administration of r-hirudin for CPB anticoagulation has previously been reported, many questions persist concerning the best therapeutic regimen for CPB anticoagulation as well as the time of onset and the doses for postoperative anticoagulation.. A 65-yr-old man was admitted for surgery of aortic stenosis after an episode of acute pulmonary edema complicated by deep venous thrombosis in the context of documented HIT. The patient received r-hirudin for 13 dy before surgery at doses (0.4 mg x kg(-1) bolus followed by 0.15 mg x kg(-1) x hr(-1) continuous infusion) that maintained activated partial thromboplastin time (aPTT) ratios between 2 and 2.5. Anticoagulation for CPB was performed with r-hirudin given as 0.1 mg x kg(-1) i.v. bolus and 0.2 mg kg(-1) in the CPB priming volume. Anticoagulation during CPB was monitored with the whole blood activated coagulation time and ecarin clotting time (ECT) performed in the operating room with values corresponding to r-hirudin concentrations >5 microg x ml(-1) during CPB. Anticoagulation during CPB was uneventful. Two bleeding episodes, related to the r-hirudin regimen and necessitating allogeneic blood transfusion, occurred after surgery.. This case report confirms previous experience of the use of r-hirudin for anticoagulation during CPB and provides additional information in the context of prolonged r-hirudin infusion before and after CPB.

Topics: Aged; Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Blood Coagulation; Blood Transfusion; Cardiopulmonary Bypass; Endopeptidases; Fibrinolytic Agents; Follow-Up Studies; Heart Valve Prosthesis Implantation; Heparin; Hirudin Therapy; Hirudins; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Postoperative Hemorrhage; Recombinant Proteins; Thrombocytopenia; Venous Thrombosis; Whole Blood Coagulation Time